TY - JOUR
T1 - Short-term biomarkers of tumor promotion in mouse skin treated with petroleum middle distillates
AU - Walborg, Earl F.
AU - DiGiovanni, John
AU - Conti, Claudio J.
AU - Slaga, Thomas J.
AU - Freeman, James J.
AU - Steup, David R.
AU - Skisak, Christopher M.
N1 - Funding Information:
preparation of the manuscript. This research was sponsored by the Middle Distillate Consortium of the American Petroleum Institute (API) with funding derived from the following companies: Amoco Oil Company, ARCO, BP Oil Company, Chevron Research and Technology, Exxon Biomedical Sciences, Inc., Lyondell-Citgo Refining Co., Pennzoil Products Company, Phillips Petroleum Company, Shell Oil Company, Sun Refining and Marketing Co., Texaco, Inc., The Unocal Company, and Witco Corporation. The able coor- FIG. 1. Relationship of biomarkers of epidermal hyperplasia and skin tumor promotion in CD-1 mice exposed topically to neat doses of API 81-07, API 81-10, and LRPO. The biomarkers of epidermal hyperplasia include induction of epidermal cell proliferation measured as an increase in the labeling (BrdUrd) index of epidermal cells and the induction of epidermal ornithine decarboxylase activity. Hyperplasiogenic responses are expressed relative to that produced by 13.6 nmol TPA.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1998/10
Y1 - 1998/10
N2 - Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that precluded any meaningful analysis of short-term biomarkers in relationship to biological activity.
AB - Topical application of certain petroleum middle distillates (PMD) to mice produces skin tumors after long latency, and initiation/promotion protocols indicate that this effect is associated with their tumor promoting activity. Since induction of sustained, potentiated epidermal hyperplasia is predictive of promoting activity, five compositionally distinct PMD [hydrodesulfurized kerosene (API 81-07); hydrodesulfurized PMD (API 81-10); odorless light petroleum hydrocarbons; severely hydrotreated light vacuum distillate (LVD); and lightly refined paraffinic oil (LRPO)] were assessed for their effects on epidermal hyperplasia. PMD were administered (2x/week for 2 weeks) to skin of CD-1 mice. Four quantitative biomarkers of epidermal hyperplasia were evaluated: epidermal thickness, number of nucleated epidermal cells per unit length of basement membrane, labeling (BrdUrd) index of epidermal cells, and induction of epidermal ornithine decarboxylase (ODC) activity. As positive controls, 12-O-tetradecanoylphorbol-13-acetate (TPA) and n-dodecane were utilized. PMD-induced skin irritation was evaluated visually and/or histopathologically. All five PMD produced dose-dependent, skin irritation and epidermal hyperplasia. On a weight basis the magnitude of the maximal PMD-induced effects was similar to that produced by n-dodecane, but > 1000-fold less than that produced by TPA. Epidermal hyperplasia and subacute skin irritancy produced by the five PMD were similar. Of the four short-term markers of tumor promotion assessed, labeling index and epidermal ODC activity were predictive of the relative promoting activities of those PMD for which tumorigenicity bioassay data are available, i.e., API 81-07 > API 81-10 > LRPO. An apparent discrepancy to the predictability of epidermal ODC activity occurred with LRPO:toluene [1:1 (v/v)]. This mixture is nontumorigenic, yet significantly induced epidermal ODC activity. This mixture, however, produced severe epidermal toxicity that precluded any meaningful analysis of short-term biomarkers in relationship to biological activity.
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U2 - 10.1006/toxs.1998.2534
DO - 10.1006/toxs.1998.2534
M3 - Article
C2 - 9848120
AN - SCOPUS:3643134255
VL - 45
SP - 137
EP - 145
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 2
ER -